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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 113  |  Issue : 1  |  Page : 14-21

Electrophysiological findings of Bardet–Biedl syndrome: a case series


Departement of Ophthalmology, Benha Faculty of Medicine, Benha University, Benha, Egypt

Date of Submission21-Dec-2019
Date of Acceptance17-Feb-2020
Date of Web Publication15-May-2020

Correspondence Address:
MD Marwa A Tabl
1 El Amira Fawzya Street, El Vilal, Banha, El Qalubyai, 13512
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejos.ejos_73_19

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  Abstract 

Background Bardet–Biedl syndrome (BBS) is a very rare autosomal recessive genetic disease with multiple manifestations including the ocular system.
Aim This study presents different electrophysiological and clinical findings in three female patients with BBS.
Patients and methods 3 female patients (9, 10 and 16 years old) with BBS were complaining of progressive visual loss. Full ophthalmological examination, optical coherence tomography (OCT) and various electrophysiological tests were performed to the 3 cases.
Results The fundoscopic findings in all three patients did not show evidence of obvious characteristic signs of retinitis pigmentosa. They presented clinically with atypical form of pigmentary retinal dystrophy. Flash electroretinogram showed severe form of Rod-cone dystrophy in the 3 cases associated with macular dysfunction evident by reduced amplitude and increased implicit time of P1 wave of the multifocal electroretinogram in all rings. The pattern electroretinogram was with poor formed P50 wave. Pattern visual evoked potential showed prolonged latency and reduced amplitude of P100 wave in large and small checks.
Conclusion Very reduced flash and multifocal electroretinogram is a Characteristic electrophysiological finding in BBS, which may precede the funduscopic changes, electrophysiological tests may help in the early diagnosis of such cases.

Keywords: flash electroretinogram, multifocal electroretinogram, rod-cone dystrophy, visual evoked potential


How to cite this article:
Tabl MA. Electrophysiological findings of Bardet–Biedl syndrome: a case series. J Egypt Ophthalmol Soc 2020;113:14-21

How to cite this URL:
Tabl MA. Electrophysiological findings of Bardet–Biedl syndrome: a case series. J Egypt Ophthalmol Soc [serial online] 2020 [cited 2020 Oct 21];113:14-21. Available from: http://www.jeos.eg.net/text.asp?2020/113/1/14/284342


  Introduction Top


Bardet–Biedl syndrome (BBS) is a very rare ciliopathic autosomal recessive genetic disease that has multiple manifestations in different body systems. Family history of consanguinity increases the risk of such disease. It was first described as Laurence–Moon–Bardet–Biedl syndrome however, later they are recognized as two distinct syndromes with similar genetic mutations [1],[2].

A progressive visual impairment due to pigmentary retinopathy is an early clinical feature of this disorder. Individuals with BBS lose their vision and most are considered as legally blind by early teens. BBS affects the cilia which are essential factors maintain healthy retinal cells [3],[4].

Variable degrees of clinical manifestations can present within the affected subjects and even among the same family. The main features of such disease include retinal degeneration, truncal obesity, polydactyly (extra toes or fingers), intellectual or learning disability, male hypogonadism, female genitourinary abnormalities, and renal dysfunction [5],[6]. BBS may also be associated with secondary features such as cataracts, astigmatism, squint, short stature, diabetes mellitus, high blood pressure, polydipsia/polyuria (diabetes insipidus), and neurological problems (e.g. ataxia or gait incoordination) [7],[8].

BBS can be resulted from mutations in different genes. There are about 21 genes (called BBS genes) have been identified until now [2].

The aim of this study was to report different electrophysiological and clinical findings in three cases of BBS.


  Patients and methods Top


Three female patients (9, 10, and 16-year olds) with BBS were included in this case series study. The participants were recruited from the outpatients’ clinics of Banha university hospital. Approval for the study was obtained from the University Local Ethics Committee and informed consent forms were signed by all participants in accordance with the requirements of the Declaration of Helsinki. The main reason for referral was abnormal low vision.

After full ophthalmologic examination, electrophysiological tests, for example, full-field electroretinogram (ERG), multifocal electroretinogram (mf-ERG), pattern electroretinogram (PERG), and pattern visual evoked potential were performed without sedation or anesthesia and following the standard clinical protocols for the International Society for Clinical Electrophysiology of Vision. Electrophysiological tests were performed with the RETI-port/scan 21 (Roland Consult, Brandenburg, Germany).

Cross‐sectional images across the macula were recorded using spectral domain optical coherence tomographers (Topcon 3D OCT model 2000 FA version 8.30, Topcon Corporation Campany, Tokyo, Japan).


  Results Top


Case 1

A 10-year-old female patient, who complained of poor central and night vision with a family history of consanguinity. Characteristic external features include obesity, polydactyly, hypertelorism, deep-set eyes, and flat nasal bridge ([Figure 1]).
Figure 1 Clinical features of the patient (case 1): face features, truncal obesity, polydactyly, and scar after removal of extra finger.

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The fundus appearance ([Figure 2]a) was with subtle changes with no obvious characteristic signs of retinitis pigmentosa. There was slight arterial attenuation with absence of the pigment spicules, but the optic disk was very pale in both eyes. The SD-OCT ([Figure 2]b) showed generalized foveal and retinal thinning. The outer nuclear layer was more thinned, and the photoreceptor inner segment/outer segment was disrupted.
Figure 2 Clinical findings of the patient (case 1): (a) fundus image, and (b) the SD-OCT.

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In this case the electrophysiological findings ([Figure 3]) confirmed the diagnosis of a severe form of rod/cone dystrophy, a retinitis pigmentosa-like picture. The full‐field flash ERG was with markedly reduced scotopic and abnormal photopic responses, with more severe affection in the rod more than the cone function. The dark‐adapted dim flash 0.01 (rod response) was very reduced; also, the maximum combined dark‐adapted response (0.3) was delayed and was with diminished a‐wave and b‐wave which indicate poor phototransduction. The photopic responses were delayed and with reduced amplitude. mfERG showed reduced P1 amplitude in all rings. The pattern VEP showed poorly formed P100 wave with prolonged latency and reduced amplitude ([Figure 4]).
Figure 3 (a) Standard full-field flash electroretinogram in Case 1: both eyes with marked reduction of all responses and (b) flash electroretinogram in a normal participant.

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Figure 4 (a) The pattern VEP of Case 1: p100 wave in both eyes with prolonged latency and reduced amplitude and (b) pattern VEP of a normal participant.

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Cases 2 and 3

Two sisters (9-years and 16-years old) were complaining of night blindness with defective vision associated with obesity, short stature, and intellectual/learning disability. The oldest girl had scar in her feet due removal of extra toes. The youngest girl with short (brachydactyly), curved (clinodactyly) outer fingers with mild webbing (syndactyly) ([Figure 5]).
Figure 5 Clinical features for patients (cases 2–3): face features, truncal obesity, scar after removal of extra toes.

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The refraction of the two girls showed astigmatic error in both eyes (−1.5 and −2.00 D, respectively). BCVA is (OD o.2, OS o.3) in the youngest girl and (OD o.1, OS o.2) in the oldest girl. The fundus picture shows slight pallor of both optic disks, slightly attenuated blood vessels, loss of foveal reflex, and few peripheral pigmentary changes with retinal pigment epithelium (RPE) atrophy ([Figure 6]). OCT shows bilateral retinal thinning, subfoveal retinal photoreceptor atrophy, with disruption of the inner segment/outer segment ([Figure 7]).
Figure 6 Fundus pictures of patients (cases 2–3).

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Figure 7 Spectral Domain optical coherence tomography (SD-OCT) of patients (cases 2–3).

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The electrophysiological tests of (cases 2–3) showed very reduced extinguished scotopic and photopic responses of the flash ERG, indicating a severe form of rod/cone dystrophy ([Figure 8]). mfERG showed very reduced P1 wave amplitude in all rings ([Figure 9]). PERG showed a very reduced amplitude of the P50 wave. Pattern VEP showed reduced amplitude of the p100 wave with prolonged latency ([Figure 10]).
Figure 8 The standard full-field flash electroretinogram in case 2: both eyes with severe reduction of all responses.

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Figure 9 The multifocal electroretinogram of case 3 shows reduced P1 amplitude in all rings with lost central foveal peak.

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Figure 10 Pattern visual evoked potential (PVEP) and pattern electroretinogram of case 3 show very reduced and delayed responses.

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  Discussion Top


BBS is a very rare autosomal recessive inherited disease. Family history of consanguinity has been reported to increase the frequency of such syndrome [8],[9].

The diagnostic criteria of BBS were established by Stigglebout and colleagues, who reported that the presence of four main features or combined three main and two secondary features are essential for the diagnosis of such syndrome. The main features are: obesity, renal abnormalities, retinal rod/cone dystrophy, postaxial polydactyly, intellectual/learning disabilities, and male hypogonadism. The secondary features are: cataract, squint, astigmatism, brachydactyly, speech disorder, syndactyly, diabetes mellitus, diabetes insipidus, teeth abnormalities, high palate, short stature, hypertension, congenital heart problems, liver dysfunction, ataxia, and gait incoordination [9],[10],[11].

An atypical form of pigmentary retinal dystrophy is a characteristic fundoscopic finding of BBS associated with early macular dysfunction. The function of rods and cones is severely affected at early stages of BBS. El-Fayoumi et al. [12] reported that 70% of their studied patients had attenuated blood vessels, 35% had optic disk pallor, and 35% of the cases had peripheral pigmentations. In another study by Berezovsky et al. [13] they stated that 67% of the patients had attenuated blood vessels; optic disk pallor was seen in 42.8%, and abnormal pigmentation was seen in 23.8%.

Few previous researches have studied the ERG changes in BBS, and they reported varied electrophysiological findings. One study reported dysfunction of both retinal rods and cones in some cases, dysfunction of only rods in selected cases and extinguished flash ERG in some cases [12], whereas other studies reported severe retinal dystrophy in all cases with affection of rods and cones [13].This study reported marked affection of rods and cone responses in the flash ERG in the three cases indicating severe forms of rod/cone dystrophy associated with early macular involvement evident by reduced PERG/P50 and mfERG P1 amplitude. The pattern VEP showed prolonged latency of P100 wave with reduced amplitude which is consistent with the pale optic disk seen in such cases. Electrophysiological abnormalities may be the first ocular findings and may precede the funduscopic changes in some cases [14].

No treatment is currently available for patients with BBS, but early diagnosis is very important for visual rehabilitations and proper assessment of possible associated complications.

Genetic testing for the family members of patients diagnosed with BBS is essential to prevent the appearance of new cases.


  Conclusion Top


In conclusion, very reduced flash ERG and mfERG is a characteristic electrophysiological finding in BBS, which may precede the funduscopic changes. Electrophysiological tests may help in the early diagnosis of such cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Forsythe E, Beales PL. Bardet-Biedl syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mefford HC, Stephens K, Amemiya A, Ledbetter N, editors. GeneReviews(R). Seattle, WA: Washington; 2003.  Back to cited text no. 1
    
2.
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3.
Genetic and Rare Diseases Information Center (GARD). An NCATS Program. Bardet-Biedl syndrome. Available at: rarediseases.info.nih.gov. [accessed August 13, 2019].  Back to cited text no. 3
    
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Beales P, Elcioglu N, Woolf A, Parker D, Flinter F. New criteria for improved diagnosis of Bardet–Biedl syndrome: results of a population survey. J Med Genet 1999; 36:437–46.  Back to cited text no. 4
    
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Abd-El-Barr MM, Sykoudis K, Andrabi S, Eichers ER, Pennesi ME, Tan PL et al. Impaired photoreceptor protein transport and synaptic transmission in a mouse model of Bardet–Biedl syndrome. Vision Res 2007; 47:3394–407.  Back to cited text no. 5
    
6.
Ramji AN. Sigmoid volvulus in bardet-biedl syndrome: serendipity or a new association?. Int Surg J 2019; 6:1388–91.  Back to cited text no. 6
    
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Ross A, Beales PL, Hill J. The clinical, molecular, and functional genetics of Bardet–Biedl syndrome. In: Beales PL, Farooqi IS, O’Rahilly S, editors. Genetics of Obesity Syndromes. Oxford New York: Oxford University Press 2009. 147–148.  Back to cited text no. 7
    
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M’hamdi O, Ouertani I, Chaabouni-Bouhamed H. Update on the genetics of bardet-biedl syndrome. Mol Syndromol 2014; 5:51–6.  Back to cited text no. 8
    
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Lo KT, Remulla J, Santiago AP. Manifestations of Bardet-Biedl syndrome. Philipp J Ophthalmol 2004; 29:94–8.  Back to cited text no. 9
    
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Siopa L, Grego M, Cossa J, Pinguinha A. Bardet-Biedl syndrome. Acta Med Port 2002; 15:51–4.  Back to cited text no. 10
    
11.
Stigglebout W. The Bardet-Biedl syndrome: including Hutchinson -LaurenceMoon syndrome. In: Vinkin PJ, Bruyn GW, editors. Neuroretinal Degenerations: Handbook of Clinical Neurology. Amsterdam: North- Holland 1972. 380–412  Back to cited text no. 11
    
12.
El-Fayoumi D, Helmy R, Nabhan M, Soliman N. Visual acuity, fundus changes, and electroretinographic findings in Egyptian children with Bardet-Biedl syndrome. Delta J Ophthalmol 2016; 17:29–34.  Back to cited text no. 12
  [Full text]  
13.
Berezovsky A, Rocha DM, Sacai PY, Watanabe SS, Cavascan NN, Salomao SR. Visual acuity and retinal function in patients with Bardet-Biedl syndrome. Clinics (Sao Paulo) 2012; 67:145–149.  Back to cited text no. 13
    
14.
Spaggiari E, Salati R, Nicolini P, Borgatti R, Pozzoli U, Polenghi F. Evolution of ocular clinical and electrophysiological findings in pediatric Bardet-Biedl syndrome. Int Ophthalmol 1999; 23:61–67.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]



 

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